Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion

• Published in: The journal of clinical endocrinology and metabolism 2022-06, Vol.107 (7), p.e2729-e2737
• Main Authors: Blackwood, Sarah J, Horwath, Oscar, Moberg, Marcus, Pontén, Marjan, Apró, William, Ekblom, Maria M, Larsen, Filip J, Katz, Abram
• Format: Article
• Language: English
• Subjects: Dextrose; Ethylenediaminetetraacetic acid; Glucose; Glucose tolerance tests; insulin; Insulin resistance; insulin secretion; intravenous glucose tolerance test; Medicin och hälsovetenskap; Medicin/Teknik; Medicine/Technology; mitochondrial respiration; muscle fiber type; Muscle proteins; Myosin; Type 2 diabetes
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgac221

Muscle fiber composition is associated with peripheral insulin action. We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia. Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group 1 (n = 11), area occupied by type I muscle fibers = 61.0 ± 11.8%, and group 2 (n = 8), type I area = 36.0 ± 4.9% (P < 0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition, and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity, and secretion were determined. Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group 2 vs group 1 (P = 0.019). First-phase insulin release (area under the insulin curve during 10 minutes after glucose infusion) was increased by almost 4-fold in group 2 vs group 1 (P = 0.01). Whole-body insulin sensitivity was correlated with percentage area occupied by type I fibers (r = 0.54; P = 0.018) and capillary density in muscle (r = 0.61; P = 0.005) but not with mitochondrial respiration. Insulin release was strongly related to percentage area occupied by type II fibers (r = 0.93; P < 0.001). Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose-stimulated insulin secretion prior to onset of clinical manifestations.